Fetal T cells are first responders to infection in adults

Fetal immune cells have specialized roles during infection

Victor Segura and Rita Serda/NIH T cells (pink) scanning host cells (green) for evidence of infection.
Victor Segura and Rita Serda/NIH T cells (pink) scanning host cells (green) for evidence of infection.

According to a new study by the Cornell scientists, there is a division of work among resistant cells that battle attacking pathogens in the body. Scientists discovered that the fetal immune cells are present in adults and have particular roles amid disease. In fact, the first immune cells made in early life are fast-acting first responders to microbes in adulthood.

These immune cells – called CD8+ T cells – come in fetal and adult varieties, which start in partitioned parts of the body and are hardwired with inherently extraordinary properties. The present worldview is that, around the time of birth, the body changes from making and utilizing fetal T cells to adult T cells to safeguard itself. Yet, Cornell scientists utilized a one of a kind report to demonstrate that fetal T cells endure into adulthood and have different roles in comparison to adult cells in battling an infection.

The first stem cells that colonize the fetal thymus come from the fetal liver and give rise to fetal T cells. Around the time of birth, a new wave of stem cells is made in the bone marrow, which then colonizes the thymus and gives rise to adult T cells.

Brian Rudd, associate professor of immunology in the College of Veterinary Medicine said, “This discovery has led to the new idea that we might be able to predict how individuals will respond to infection based on how many fetal cells are present in the adult pool and isolate the fast-acting fetal-derived cells for certain therapeutic interventions, such as infections and cancer immunotherapy.”

“What we found is that fetal and adult T cells are intrinsically different. The reason for that is they derive from different stem cells, which are genetically distinct.”

In adults, newly shaped T cells perceive a signature protein on a pathogen when they first encounter it. That signal at that point actuates the T cells and prepares them to battle and multiply up to 15 times, creating up to 10 million cells in a week. Once the pathogen has been cleared, the majority of those adult T cells die, yet up to 10 percent survive and are put away in a pool of memory cells, taking into account a fast recall response if that same pathogen were to strike once more.

Fetal-determined cells, then again, are generalists and don’t shape into memory cells. They react to inflammatory signals and initiate quicker than adult T cells, enabling them to give a broad swath of security against pathogens they don’t particularly perceive.

Rudd said, “It’s the way that the immune system hedges its bet: It has cells that can respond at different rates.”

During the study, scientists used a special “time-stamp” mouse that allowed them to map the fate of these cells throughout the mouse’s life. A drug (tamoxifen) injected at various stages of life marks the waves of T cells made during different stages of development. The system allowed the researchers to see which cells were present during adulthood.

Rudd said, “We were able to map cells produced at different stages of life and track their numbers and functions over the lifespan. This led to the discovery that there are developmental layers to an immune response, which has previously gone unnoticed.”

Co-authors include researchers from Andrew Grimson’s lab in the Department of Molecular Biology and Genetics and mathematicians from Miles Davenport’s lab at the University of New South Wales in Sydney, Australia.

The study is published June 14 in the journal Cell.